Current therapeutic approaches for epilepsy primarily represent symptomatic treatments that suppress seizures, but have not been demonstrated to prevent epilepsy or modify disease progression. In recent years, there have been tremendous interest in developing disease-modifying or antiepileptogenic therapies. Tuberous Sclerosis Complex (TSC) is a common genetic cause of epilepsy and a subset of TSC patients rnay represent a rational, feasible population to target an antiepileptogenic treatment approach. First of all, some patients are diagnosed with TSC at a young age before the onset of epilepsy due to the presence of non-neurological findings: The presence of these findings makes it feasible to identify these patients and initiate a potential antiepileptogenic treatment at an early stage of epileptogenesis. Second, these patients are at high risk for developing epilepsy in the future. Because of these factors initiating a therapy with potential side effects in a presymptomatic stage can likely be justified in TSC patients. Finally, the identification of the mTOR pathway in the pathophysiology of TSC suggests that mTOR inhibitors could have antiepileptogenic properties in TSC but there may be significant risks and side effects. Therefore, before initiating an antiepileptogenic drug trial in TSC patients, it would be beneficial to obtain further evidence to optimize the selection criteria and treatment paradigms to maximize efficacy and minimize side effects of mTOR inhibitors, as well as establish a network of preclinical and clinical sites. In this P20 grant application we propose to conduct pre-clinical and clinical studies that establish optimal parameters for a potential antiepileptogenic drug trial. The preclinical core will aim to determine the optimal rapamycin treatment paradigms that maintain antiepileptogenic efficacy but minimize risks of side effects. The clinical core aims to determine whether EEGs during infancy are a reliable biomarker to identify TSC patients that will develop epilepsy and thus appropriate candidates for an antiepileptogenic drug trial. We will also establish the infrastructure for a TSC Epilepsy Center Without Walls, which will facilitate such clinical trials.